Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The neighborhood matters: Packard Center scientists show cell environment is important in ALS

06.10.2003


In amyotrophic lateral sclerosis (ALS), neighborhood may be everything, if a new study in mouse models of the disease holds true for patients.



ALS, or Lou Gehrig’s disease, brings about a gradual death of the motor neurons that activate muscles. Paralysis follows. But according to work described today in the journal Science, the cells that are next to motor neurons -- but aren’t themselves nerve cells -- can play a major role in advancing or limiting the disease.

"What we’ve been given is a new principle for extending survival or, perhaps, overcoming ALS, based on how many healthy cells surround an ailing motor nerve cell," says Don Cleveland, Ph.D., a scientist with The Packard Center for ALS Research at Johns Hopkins and, with Larry Goldstein, Ph.D., co-leader of the research team. "All this has great implications for stem cell therapy," he adds. "We now believe delivery of normal, non-neuronal cells to spinal cords could be completely protective, even without replacement of a single motor neuron."


In a series of experiments, the team measured the effect of having different proportions of healthy cells to at-risk cells in mice, clocking their survival time. Normally, the scientists work with standard animal models of ALS. Those mice or rats carry a mutant human gene -- called SOD1 -- that triggers a rare, inherited form of the disease in people. In these models, every cell carries a mutant SOD1 gene. The animals typically slip into death by the time they’re six to eight months of age.

But in this study, the researchers used chimeric animals -- mice engineered to be a mix of normal cells, also called wild type, and cells containing the mutant SOD1 gene. They tagged the cells with molecular flags to make it clear which were which. The percent of wild-type cells in the animals’ spinal cords ranged from 5 to 90 percent.

Having wild type cells mixed in had the effect of extending mouse survival from one to eight months, depending on the number of cells and type of SOD1 mutation. In a second group of chimeric mice, brought about by a different technique and with a different type of tracer, the animals survived disease-free until sacrificed for study at an age at least twice the age at which typical SOD1 animal models die.

Even though further study showed that as high as three-fourths of the motor neurons in the animals’ spinal cords carried the mutant gene, all the motor neurons remained amazingly healthy, apparently from having healthy non-neuronal cells in the neighborhood. This was especially true of the second batch of mice, which had no microscopic evidence of disease.

"It’s really striking," says Cleveland, "to see what a small number of normal cells effectively eliminated damage to motor neurons from the ALS-causing genetic error."

The opposite effect also appeared: mice with normal motor neurons but with surrounding cells carrying an SOD1 mutation showed early signs of disease. Normal neurons, then, can apparently acquire something toxic from at-risk non-neuronal neighboring cells.

"So we’re seeing a real-life metaphor here," says Cleveland. "Living in a bad environment can damage good cells. And more important, restoring a better environment to ’bad’ neurons by surrounding them with healthy neighbors can significantly lessen toxic effects. In some cases, having normal cells completely stops motor neuron death."

Research conducted by Center scientist and team member Jean-Pierre Julien, Ph.D., at Laval University in Quebec was a key contribution to the results. Researchers Cleveland and Goldstein are both at the University of California, San Diego, where Cleveland heads the Laboratory of Cell Biology at the Ludwig Institute for Cancer Research.

The research was funded by the Packard Center for ALS Research at Johns Hopkins, Project ALS, The ALS Association, the U.S. National Institutes of Health, the Canadian Institutes of Health Research, The Angel Fund for ALS Research and the U.S. Veterans Administration.

Headquartered in Baltimore, the Robert Packard Center for ALS Research at Johns Hopkins is a collaboration of scientists worldwide who are working aggressively to develop new treatments and a cure for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The Center is the only institution of its kind dedicated solely to the disease. Its research is meant to translate from the laboratory bench to the clinic in record time.

Joanna Downer | EurekAlert!
Further information:
http://www.hopkinsmedicine.org/

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>